Tendon injuries, particularly sports-related injuries, constitute an increasing proportion of cases treated at our hospital, yet research in the molecular and cell biology of tendon healing is in its embryonic stages. Morphological, biomechanical and biochemical studies of normal tendon have revealed fundamental architecture, that exercise enhances healing and that fewer collagen crosslinks can be correlated with increased range of motion during convalescence after tendon injury. The overall objective of this study is to establish, on the molecular level, how exercise alters the metabolism of tendon cells to yield the proper balance between cell division and matrix production resulting in a healed tendon that is strong yet flexible. Results of recent experiments in this laboratory indicate that aortic endothelial cells respond to a repeating stress cycle of 10 sec 10% elongation and 10 sec relaxation in vitro by increasing their rate of division. The same stress regimen decreases the division rate of tendon fibroblasts. These different responses to the same stress field seem reasonable given that endothelial cells need to completely cover the interior of a blood vessel and regulate transport, but do not contribute much mechanical strength, whereas an organ such as tendon requires great tensile strength to transmit the force of muscle contraction to bone effect limb movement. In this case, if tendon became highly cellular, it would have insufficient mechanical strength to perform its work. Hence cyclic stress to tendon probably results in matrix production and not cell division. The important conclusion is that the response to physical stress probably varies for each tissue and may depend on the nature of the stress as well as the cell type affected. It should be possible to define what regimen activates a given cell to produce one of two principle effects: an alteration in cell division or matrix production. It is most likely that rapid changes in cells, occurring in secs or mins, could be involved in signal reception or transduction related to the magnitude of the stress. Slower responses involved in long term reactions would involve whether or not cells divide or produce matrix resulting in tissue build-up or degradation affecting the ultimate strength and flexibility of the tissue. In this proposal, I intend to correlate cell metabolism and matrix qualities of living tendon subjected to exercise or immobilization, the two extremes of applied force in vivo with those of cells subjected to applied force in vitro.